Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy

The metabolic syndrome-a collection of factors associated with increased risk for cardiovascular disease and diabetes-is becoming increasingly common, largely as a result of the increase in the prevalence of obesity. Although it is generally agreed that first-line clinical intervention for the metabolic syndrome is lifestyle change, this is insufficient to normalize the risk factors in many patients, and so residual risk could be high enough to justify drug therapy. However, at present there are no approved drugs that can reliably reduce all of the metabolic risk factors over the long term, and so there is growing interest in therapeutic strategies that might target multiple risk factors more effectively, thereby minimizing problems with polypharmacy. This review summarizes current understanding of the nature of the metabolic syndrome, and discusses each of the risk factors of the metabolic syndrome as possible primary drug targets; potential secondary or tertiary targets are also considered.